用TERN-501单疗法和与TERN-101结合治疗代谢功能障碍相关的脂肪肝炎:随机二期a DUET试验
Mazen Noureddin1, Naim Alkhouri2, Eric J Lawitz3
1Houston Methodist Hospital, Houston Research Institute, Houston, TX, USA. NoureddinMD@houstonresearchinstitute.com.
Nature medicine
|June 11, 2025
概括
甲状腺激素受体-β (THRβ) 激动剂TERN-501显著减少MASH患者的肝脂肪. 该药物表现出剂量依赖的效果,较高剂量显示肝脏脂肪含量减少较大,与安慰剂相比.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 代谢功能障碍相关的脂肪肝炎 (MASH) 是一个重要的未满足的医疗需求.
- 甲状腺激素受体-β (THRβ) 激动症是MASH的有前途的治疗策略.
- 针对多个途径的双重激应可能会提高疗效.
研究的目的:
- 评估TERN-501的疗效和安全性,一个THRβ激动剂,作为单一治疗和与TERN-101 (FXR激动剂) 结合治疗MASH患者.
- 评估TERN-501对肝脏脂肪减少的剂量依赖作用.
主要方法:
- 一个为期12周的,随机的,双盲的,安慰剂控制的,多中心的2a期研究 (DUET).
- 162名疑似MASH患者被随机分配到TERN-501单疗法 (1,3或6毫克),TERN-101单疗法 (10毫克),组合疗法 (TERN-501 + TERN-101) 或安慰剂.
- 主要终点:12周肝脏脂肪含量的相对变化 (MRI-PDFF) 与基线相比.
主要成果:
- TERN-501 显示了剂量依赖的肝脏脂肪的减少.
- 在第12周的MRI-PDFF中最小平方平均变化为: -15.4% (1 mg), -27.5% (3 mg,P=0.0036),和-44.8% (6 mg,P<0.0001) 与安慰剂组的-4.0%.
- 在TERN-501单疗和安慰剂组中,不良事件发生率相似.
结论:
- 在MASH患者中,TERN-501单一治疗导致肝脂肪的显著,剂量依赖的减少.
- TERN-501的安全概况与安慰剂可比.
- 需要对MASH的THRβ激动性进行进一步的研究.
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